Birt–Hogg–Dubé syndrome

Overview

Birt–Hogg–Dubé syndrome (BHD) is a rare, inherited genetic disorder that primarily affects the skin, lungs, and kidneys. It is characterized by the development of benign skin tumors called fibrofolliculomas, lung cysts that can lead to spontaneous pneumothorax (collapsed lung), and an increased risk of developing various types of kidney tumors. The condition was first described in 1977 by doctors Birt, Hogg, and Dubé. BHD is an autosomal dominant disorder, meaning a mutation in just one copy of the responsible gene can cause the syndrome.

Causes

Birt–Hogg–Dubé syndrome is caused by mutations in the FLCN gene, which encodes a protein called folliculin. Folliculin is thought to play a role in cell growth, energy sensing, and tumor suppression. When mutations occur in this gene, the regulation of cell growth is disrupted, leading to the development of tumors and cysts in affected tissues. Because it is inherited in an autosomal dominant pattern, individuals with one mutated copy of the gene have a 50% chance of passing the condition on to their offspring.

Symptoms

The signs and symptoms of Birt–Hogg–Dubé syndrome can vary widely, even within the same family. Common manifestations include:

• Skin lesions (fibrofolliculomas) – small, dome-shaped, whitish bumps usually appearing on the face, neck, and upper trunk

• Lung cysts – fluid- or air-filled sacs that increase the risk of spontaneous pneumothorax (collapsed lung)

• Spontaneous pneumothorax – sudden chest pain and shortness of breath due to a collapsed lung, often requiring medical attention

• Kidney tumors – benign or malignant tumors; individuals with BHD are at an increased risk of developing renal cell carcinoma, often multifocal or bilateral

Diagnosis

Diagnosis of BHD is based on clinical findings, family history, imaging studies, and confirmed by genetic testing. Diagnostic steps typically include:

• Clinical examination – evaluation of skin lesions and family history of similar symptoms

• CT scan or high-resolution imaging of the chest – to identify lung cysts

• Abdominal MRI or CT scan – to screen for kidney tumors

• Skin biopsy – to confirm the presence of fibrofolliculomas

• Genetic testing – confirmation of mutations in the FLCN gene

Treatment

There is no cure for Birt–Hogg–Dubé syndrome, so treatment focuses on managing symptoms and monitoring for complications. Key aspects of management include:

• Dermatologic care – laser therapy or surgical removal of skin lesions for cosmetic reasons, though recurrence is common

• Management of pneumothorax – including observation, chest tube insertion, or surgical intervention such as pleurodesis to prevent recurrence

• Surveillance for kidney tumors – regular imaging (usually MRI or CT) starting in early adulthood, typically every 1–2 years

• Surgical removal of kidney tumors – nephron-sparing surgery is preferred to preserve kidney function

• Genetic counseling – for affected individuals and their families

Prognosis

With appropriate monitoring and treatment, individuals with Birt–Hogg–Dubé syndrome can live relatively normal lives. The most serious health risks are associated with kidney tumors, which can be life-threatening if not detected and treated early. Spontaneous pneumothorax, while potentially serious, can often be effectively managed. Regular follow-up and multidisciplinary care are essential to reduce complications and improve long-term outcomes.